Role of Metal Ions in the Self-assembly of the Alzheimer’s Amyloid-β Peptide

2013 ◽  
Vol 52 (21) ◽  
pp. 12193-12206 ◽  
Author(s):  
Peter Faller ◽  
Christelle Hureau ◽  
Olivia Berthoumieu
Keyword(s):  
Metal Ions ◽  
Self Assembly ◽  
Amyloid Β ◽  
The Self ◽  
Amyloid Β Peptide

scholarly journals Metal ion coordination delays amyloid-β peptide self-assembly by forming an aggregation–inert complex

2020 ◽  
Vol 295 (21) ◽  
pp. 7224-7234 ◽  
Author(s):  
Cecilia Wallin ◽  
Jüri Jarvet ◽  
Henrik Biverstål ◽  
Sebastian Wärmländer ◽  
Jens Danielsson ◽  
...  
Keyword(s):  
Metal Ions ◽  
Self Assembly ◽  
Metal Ion ◽  
Amyloid Β ◽  
Bound State ◽  
Ion Binding ◽  
Amyloid Β Peptide ◽  
Aβ Peptide ◽  
Metal Ion Binding

A detailed understanding of the molecular pathways for amyloid-β (Aβ) peptide aggregation from monomers into amyloid fibrils, a hallmark of Alzheimer's disease, is crucial for the development of diagnostic and therapeutic strategies. We investigate the molecular details of peptide fibrillization in vitro by perturbing this process through addition of differently charged metal ions. Here, we used a monovalent probe, the silver ion, that, similarly to divalent metal ions, binds to monomeric Aβ peptide and efficiently modulates Aβ fibrillization. On the basis of our findings, combined with our previous results on divalent zinc ions, we propose a model that links the microscopic metal-ion binding to Aβ monomers to its macroscopic impact on the peptide self-assembly observed in bulk experiments. We found that substoichiometric concentrations of the investigated metal ions bind specifically to the N-terminal region of Aβ, forming a dynamic, partially compact complex. The metal-ion bound state appears to be incapable of aggregation, effectively reducing the available monomeric Aβ pool for incorporation into fibrils. This is especially reflected in a decreased fibril-end elongation rate. However, because the bound state is significantly less stable than the amyloid state, Aβ peptides are only transiently redirected from fibril formation, and eventually almost all Aβ monomers are integrated into fibrils. Taken together, these findings unravel the mechanistic consequences of delaying Aβ aggregation via weak metal-ion binding, quantitatively linking the contributions of specific interactions of metal ions with monomeric Aβ to their effects on bulk aggregation.

Ligand Constraints and Synthesis of Metal–Organic Polyhedra

2015 ◽  
Vol 68 (5) ◽  
pp. 707 ◽  
Author(s):  
Harsh Vardhan ◽  
Francis Verpoort
Keyword(s):  
Metal Ions ◽  
Self Assembly ◽  
Three Dimensional ◽  
The Self ◽  
Bend Angle ◽  
Metal Organic ◽  
Discrete Structures ◽  
Hydrophobic Nature ◽  
Internal Volume

Metal–organic polyhedra are three dimensional discrete structures typically constructed by the self-assembly of metal ions and ligands. The synthesis and geometry of discrete structures entirely rely on the choice of metal ions, ligand constraints such as steric bulk, bend angle, and functionalities, and the nature of applied solvents. As a result, they provide tailorable internal volume and usually hydrophobic nature to the cavity that in turn makes them one of the prominent host molecules for a range of applications. This review highlights the intervention of ligand constraints, precisely bend angle (0°, 60°, 120°, and 180°), hydroxyl functionalities, and the role of concepts such as molecular panelling and subcomponent self-assembly in the synthesis of polyhedra.

scholarly journals Unravelling the role of amino acid sequence order in the assembly and function of the amyloid-β core

2019 ◽  
Vol 55 (59) ◽  
pp. 8595-8598 ◽  
Author(s):  
Santu Bera ◽  
Elad Arad ◽  
Lee Schnaider ◽  
Shira Shaham-Niv ◽  
Valeria Castelletto ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Self Assembly ◽  
Amyloid Β ◽  
The Self ◽  
Biological Functions ◽  
The Core ◽  
Recognition Motif ◽  
And Function

Here we report the influence of amino acid sequence order on the self-assembly and biological functions of the core recognition motif of Amyloid β.

Directive Effect of Chain Length in Modulating Peptide Nano-assemblies

2020 ◽  
Vol 27 (9) ◽  
pp. 923-929
Author(s):  
Gaurav Pandey ◽  
Prem Prakash Das ◽  
Vibin Ramakrishnan
Keyword(s):  
Electron Microscopy ◽  
Amino Acids ◽  
Light Scattering ◽  
Chain Length ◽  
Self Assembly ◽  
The Self ◽  
Ionic Charge ◽  
Self Assembling ◽  
Biophysical Techniques

Background: RADA-4 (Ac-RADARADARADARADA-NH2) is the most extensively studied and marketed self-assembling peptide, forming hydrogel, used to create defined threedimensional microenvironments for cell culture applications. Objectives: In this work, we use various biophysical techniques to investigate the length dependency of RADA aggregation and assembly. Methods: We synthesized a series of RADA-N peptides, N ranging from 1 to 4, resulting in four peptides having 4, 8, 12, and 16 amino acids in their sequence. Through a combination of various biophysical methods including thioflavin T fluorescence assay, static right angle light scattering assay, Dynamic Light Scattering (DLS), electron microscopy, CD, and IR spectroscopy, we have examined the role of chain-length on the self-assembly of RADA peptide. Results: Our observations show that the aggregation of ionic, charge-complementary RADA motifcontaining peptides is length-dependent, with N less than 3 are not forming spontaneous selfassemblies. Conclusion: The six biophysical experiments discussed in this paper validate the significance of chain-length on the epitaxial growth of RADA peptide self-assembly.

scholarly journals Understanding the role of conjugation length on the self-assembly behaviour of oligophenyleneethynylenes

2021 ◽  
Author(s):  
Beatriz Matarranz ◽  
Goutam Ghosh ◽  
Ramesh Kandanelli ◽  
Angel Sampedro ◽  
Kalathil K. Kartha ◽  
...  
Keyword(s):  
Self Assembly ◽  
The Self ◽  
Conjugation Length ◽  
The Relationship

We unravel the relationship between conjugation length and self-assembly behaviour of oligophenyleneethynylenes (OPEs).

scholarly journals An evaluation of the self-assembly enhancing properties of cell-derived hexameric amyloid-β

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Devkee M. Vadukul ◽  
Céline Vrancx ◽  
Pierre Burguet ◽  
Sabrina Contino ◽  
Nuria Suelves ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Self Assembly ◽  
Critical Nucleus ◽  
Amyloid Fibril ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
The Self ◽  
Aβ Peptide ◽  
Amyloid Fibril Formation ◽  
Secretase Activity

AbstractA key hallmark of Alzheimer’s disease is the extracellular deposition of amyloid plaques composed primarily of the amyloidogenic amyloid-β (Aβ) peptide. The Aβ peptide is a product of sequential cleavage of the Amyloid Precursor Protein, the first step of which gives rise to a C-terminal Fragment (C99). Cleavage of C99 by γ-secretase activity releases Aβ of several lengths and the Aβ42 isoform in particular has been identified as being neurotoxic. The misfolding of Aβ leads to subsequent amyloid fibril formation by nucleated polymerisation. This requires an initial and critical nucleus for self-assembly. Here, we identify and characterise the composition and self-assembly properties of cell-derived hexameric Aβ42 and show its assembly enhancing properties which are dependent on the Aβ monomer availability. Identification of nucleating assemblies that contribute to self-assembly in this way may serve as therapeutic targets to prevent the formation of toxic oligomers.

scholarly journals Astrocytes and neuroinflammation in Alzheimer's disease

2014 ◽  
Vol 42 (5) ◽  
pp. 1321-1325 ◽  
Author(s):  
Emma C. Phillips ◽  
Cara L. Croft ◽  
Ksenia Kurbatskaya ◽  
Michael J. O’Neill ◽  
Michael L. Hutton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Responses ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Amyloid Β Peptide ◽  
Substantial Evidence ◽  
Models Of Disease ◽  
Opposing Effects

Increased production of amyloid β-peptide (Aβ) and altered processing of tau in Alzheimer's disease (AD) are associated with synaptic dysfunction, neuronal death and cognitive and behavioural deficits. Neuroinflammation is also a prominent feature of AD brain and considerable evidence indicates that inflammatory events play a significant role in modulating the progression of AD. The role of microglia in AD inflammation has long been acknowledged. Substantial evidence now demonstrates that astrocyte-mediated inflammatory responses also influence pathology development, synapse health and neurodegeneration in AD. Several anti-inflammatory therapies targeting astrocytes show significant benefit in models of disease, particularly with respect to tau-associated neurodegeneration. However, the effectiveness of these approaches is complex, since modulating inflammatory pathways often has opposing effects on the development of tau and amyloid pathology, and is dependent on the precise phenotype and activities of astrocytes in different cellular environments. An increased understanding of interactions between astrocytes and neurons under different conditions is required for the development of safe and effective astrocyte-based therapies for AD and related neurodegenerative diseases.

Role of Multivalent Cations in the Self-Assembly of Phospholipid−DNA Complexes

2007 ◽  
Vol 111 (51) ◽  
pp. 14233-14238 ◽  
Author(s):  
Guillaume Tresset ◽  
Wun Chet Davy Cheong ◽  
Yeng Ming Lam
Keyword(s):  
Self Assembly ◽  
The Self ◽  
Dna Complexes
Sign in / Sign up

Export Citation Format

Share Document